# Exploring mechanisms underlying SCF+G-CSF-enhanced recovery in chronic  TBI.

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2021 · $405,177

## Abstract

SUMMARY/ABSTRACT
Traumatic brain injury (TBI) represents a public health crisis in the United States. TBI is a very common injury
in young adults and causes long-term disabilities in cognition, learning and memory, emotional control, and
sensory and motor function. A severe TBI can lead to lifelong physical and psychological problems and
increase the risk of developing neurodegenerative diseases. Severe TBI in young adults is a significant public
health problem and national burden because their lifelong disabilities, permanent productivity loss, and long-
term daily care dependence not only seriously affect the life of an individual and their family but also create a
heavy financial burden in the United States.
In the traditional view, TBI is an event that only needs acute management and a brief period of rehabilitation.
Today’s notion is that TBI is the onset of a chronic health condition that requires therapies for improving
recovery months and years after TBI. However, no such a treatment is available in the chronic phase. The
chronic phase exists in a long period from 3 or 6 months after TBI and throughout an individual’s life span. The
lack of treatment to improve severe TBI recovery in the chronic phase is a critical problem for the country.
Using a severe TBI model in young adult mice, we have demonstrated significant improvements in functional
recovery by a combination treatment of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-
CSF) (SCF+G-CSF) in the chronic phase. However, it remains unclear how SCF+G-CSF treatment in the
chronic phase of severe TBI improves functional recovery. The objective of this application is to determine the
underlying mechanisms of the SCF+G-CSF-enhanced recovery in chronic TBI. Based on preliminary studies,
we hypothesize that SCF+G-CSF-improved severe TBI recovery in the chronic phase is mediated by the
enhancement of cerebral remyelination and neurostructural regeneration. Using the approaches of molecular
and cellular biology, pharmacology, Cre-LoxP technology, 2-photon live brain imaging and neurobehavioral
evaluation, this hypothesis will be tested through two Specific Aims. Aim 1 will determine how SCF+G-CSF
treatment in the chronic phase of severe TBI enhances remyelination in cerebral white matter, and Aim 2 will
define how SCF+G-CSF treatment in the chronic phase of severe TBI enhances neural structure regeneration.
Searching for treatments to improve severe TBI recovery in the chronic phase is a highly-important-but-not-
investigated field and an urgent national demand to improve the health of young adults living with severe TBI. It
is expected that the accomplishment of the proposed mechanistic studies will significantly move the TBI
research field forward by identifying a unique pharmacological approach to repair a severe TBI-damaged brain
in the chronic phase.

## Key facts

- **NIH application ID:** 10220357
- **Project number:** 1R01NS118166-01A1
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** LI-RU ZHAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,177
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220357

## Citation

> US National Institutes of Health, RePORTER application 10220357, Exploring mechanisms underlying SCF+G-CSF-enhanced recovery in chronic  TBI. (1R01NS118166-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220357. Licensed CC0.

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